UNLABELLED: The PI3K/Akt signaling pathway is constitutively activated in some pancreatic cancers; when activated, it inhibits chemotherapy-mediated apoptosis. We examined whether Akt activity correlates with apoptotic resistance to chemotherapy in pancreatic cancer. MATERIALS AND METHODS: A panel of human pancreatic cancer cells was evaluated for basal Akt activity as well as response to three chemotherapies. Chemotherapy-induced cell death was evaluated following either up- or down-regulation of Akt activity. Evaluation of phosphorylation of p21Cip/Waf1, a downstream target of Akt, was also evaluated. RESULTS: There was a broad distribution among pancreatic cancer cell lines by Akt activity, as well as sensitivity to the three chemotherapeutic agents with no apparent correlation. Phosphorylation of p21Cip/Waf1, but not change in total levels, correlated with the chemosensitizing effect of Akt inhibition to paclitaxel. CONCLUSIONS: Basal Akt activity does not appear to be a useful predictor for selection of pancreatic cancers in targeting Akt to broadly induce chemosensitivity.
UNLABELLED: The PI3K/Akt signaling pathway is constitutively activated in some pancreatic cancers; when activated, it inhibits chemotherapy-mediated apoptosis. We examined whether Akt activity correlates with apoptotic resistance to chemotherapy in pancreatic cancer. MATERIALS AND METHODS: A panel of humanpancreatic cancer cells was evaluated for basal Akt activity as well as response to three chemotherapies. Chemotherapy-induced cell death was evaluated following either up- or down-regulation of Akt activity. Evaluation of phosphorylation of p21Cip/Waf1, a downstream target of Akt, was also evaluated. RESULTS: There was a broad distribution among pancreatic cancer cell lines by Akt activity, as well as sensitivity to the three chemotherapeutic agents with no apparent correlation. Phosphorylation of p21Cip/Waf1, but not change in total levels, correlated with the chemosensitizing effect of Akt inhibition to paclitaxel. CONCLUSIONS: Basal Akt activity does not appear to be a useful predictor for selection of pancreatic cancers in targeting Akt to broadly induce chemosensitivity.
Authors: Victor M Bondar; Bridget Sweeney-Gotsch; Michael Andreeff; Gordon B Mills; David J McConkey Journal: Mol Cancer Ther Date: 2002-10 Impact factor: 6.261
Authors: M Sun; G Wang; J E Paciga; R I Feldman; Z Q Yuan; X L Ma; S A Shelley; R Jove; P N Tsichlis; S V Nicosia; J Q Cheng Journal: Am J Pathol Date: 2001-08 Impact factor: 4.307
Authors: Yan Luo; Richard A Smith; Ran Guan; Xuesong Liu; Vered Klinghofer; Jianwei Shen; Charles Hutchins; Paul Richardson; Tom Holzman; Saul H Rosenberg; Vincent L Giranda Journal: Biochemistry Date: 2004-02-10 Impact factor: 3.162
Authors: Nathan T Ihle; Robert Lemos; Peter Wipf; Adly Yacoub; Clint Mitchell; Doris Siwak; Gordon B Mills; Paul Dent; D Lynn Kirkpatrick; Garth Powis Journal: Cancer Res Date: 2009-01-01 Impact factor: 12.701